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Gut Microbes. 2017 Nov 2;8(6):589-600. doi: 10.1080/19490976.2017.1353849. Epub 2017 Aug 18.

Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig.

Author information

1
a Piglet Nutrition & Cognition Laboratory , University of Illinois , Urbana , IL , USA.
2
b Neuroscience Program , University of Illinois , Urbana , IL , USA.
3
c Division of Nutritional Sciences , University of Illinois , Urbana , IL , USA.
4
d Department of Food Science and Human Nutrition , University of Illinois , Urbana , IL , USA.

Abstract

A dynamic relationship between the gut microbiota and brain is pivotal in neonatal development. Dysbiosis of the microbiome may result in altered neurodevelopment; however, it is unclear which specific members of microbiota are most influential and what factors might mediate the relationship between the gut and the brain. Twenty-four vaginally-derived male piglets were subjected to magnetic resonance spectroscopy at 30 d of age. Ascending colon contents, feces, and blood were collected and analyzed for volatile fatty acids, microbiota relative abundance by 16s rRNA, and serum metabolites, respectively. A mediation analysis was performed to assess the mediatory effect of serum biomarkers on the relationship between microbiota and neurometabolites. Results indicated fecal Ruminococcus and Butyricimonas predicted brain N-acetylaspartate (NAA). Analysis of serum biomarkers indicated Ruminococcus independently predicted serum serotonin and cortisol. A 3-step mediation indicated: i) Ruminococcus negatively predicted NAA, ii) Ruminococcus negatively predicted cortisol, and iii) a significant indirect effect (i.e., the effect of fecal Ruminococcus through cortisol on NAA) was observed and the direct effect became insignificant. Thus, serum cortisol fully mediated the relationship between fecal Ruminococcus and brain NAA. Using magnetic resonance spectroscopy, this study used a statistical mediation analysis and provides a novel perspective into the potential underlying mechanisms through which the microbiota may shape brain development. This is the first study to link Ruminococcus, cortisol, and NAA in vivo, and these findings are substantiated by previous literature indicating these factors may be influential in the etiology of neurodevelopmental disorders.

KEYWORDS:

N-acetylaspartate; Ruminococcus; autism; microbiome; neurodevelopment; pig

PMID:
28703640
PMCID:
PMC5730385
DOI:
10.1080/19490976.2017.1353849
[Indexed for MEDLINE]
Free PMC Article

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